MEDICAL DISCLAIMER: Educational research guidelines only. Lyophilized peptides are investigational chemical compounds and are NOT approved for human consumption, diagnosis, or therapy. Consult a licensed physician before any research application.
ACE-031 Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
ACE-031 (ramatercept, ActRIIB-Fc) is a discontinued investigational fusion protein that links the soluble extracellular domain of the activin type IIB receptor to a human IgG1 Fc fragment. It works as a myostatin/activin "ligand trap," binding myostatin (GDF-8), activins, and GDF-11 in the circulation so they cannot signal through their receptors to limit muscle growth (PMID 23169607, PMID 16330774). In a Phase 1 study, a single 3 mg/kg subcutaneous dose raised lean mass by 3.3% and thigh muscle volume by 5.1% within a month. Development for Duchenne muscular dystrophy was halted in 2011 and discontinued in 2013 after the drug caused nosebleeds, gum bleeding, and skin telangiectasia, linked to off-target inhibition of the vascular regulators BMP9 and BMP10. ACE-031 is not approved anywhere, is banned by WADA, and is shown here only as an educational dosing reference, not medical advice.
Reconstitute: Add 1 mL bacteriostatic water → 1 mg/mL concentration.
Typical dose: 0.02-3 mg/kg SC every 2-4 weeks (clinical; program discontinued)
Easy measuring: At 1 mg/mL, 1 unit = 0.01 mL = 0.0100 mg (10 mcg) on a U-100 insulin syringe.
Storage: Lyophilized powder stored frozen at −20 °C; reconstituted solution refrigerated at 2-8 °C, protected from light, and used within roughly 2-4 weeks. As an Fc fusion protein, ACE-031 should not be repeatedly freeze-thawed or shaken vigorously, which can denature or aggregate it; swirl gently only.
Half-life: Approximately 10-15 days (subcutaneous; Tmax ~5-7 days), reflecting the long-acting IgG1 Fc fusion design.
Route: Subcutaneous injection in all human trials; clinical dosing was weight-based at 0.02-3 mg/kg every 2-4 weeks.
Status: Not FDA/EMA approved; development discontinued in 2013 for vascular bleeding; WADA-prohibited; research/educational use only.
About ACE-031
ACE-031 (ramatercept, ActRIIB-Fc) is an investigational soluble activin type IIB receptor fused to a human IgG1 Fc fragment. It acts as a myostatin/activin ligand trap, mopping up myostatin (GDF-8), activin A and B, GDF-11 and related TGF-beta ligands before they can engage their cell-surface receptors and limit muscle growth [1][3]. Because it is a large fusion protein, the real-world route in every human trial was subcutaneous injection on a weight-based schedule of 0.02-3 mg/kg every 2-4 weeks; the fixed-microgram figures below are an educational reconstitution reference, not a clinical regimen.\n\nA search for an \"ACE-031 dosage\" usually conflates two very different numbers: the clinical doses (0.02-3 mg/kg subcutaneously, with muscle gains seen only at the highest 3 mg/kg dose) and the much smaller fixed doses (roughly 0.25-1 mg) used with grey-market 1 mg research vials. This page models the latter so the math maps cleanly onto a U-100 insulin syringe, while making clear those small doses sit at or below the lowest clinical dose and far below the dose that actually moved muscle endpoints [1].\n\nThis guide models a 1 mg vial reconstituted with 1.0 mL of bacteriostatic water (1 mg/mL, 10 mcg per insulin-syringe unit): 250 mcg = 25 units, 500 mcg = 50 units, and 1000 mcg = 100 units (one full syringe).\n\nFrequency: Once weekly in this educational model; clinical trials dosed every 2-4 weeks because the elimination half-life is roughly 10-15 days. ACE-031 is NOT approved by the FDA or EMA — its development was discontinued in 2013 after vascular bleeding side effects — and it is presented here for educational purposes only [2][6].
Quick Protocol Navigation
Reconstitution Instruction & Mixing Step-by-Step
Lyophilized powder must be reconstituted carefully. Agitating peptide chains can shear disulfide bonds and render the peptide biologically inert.
Draw 1.0 mL of bacteriostatic water into a sterile syringe.
Inject the water slowly down the inner wall of the 1 mg ACE-031 vial so it runs onto the protein cake; do not aim the stream directly at the powder and never shake the vial, because an Fc fusion protein can foam, denature, or aggregate.
Swirl or roll the vial gently until the solution is completely clear; the result is a 1 mg/mL concentration (10 mcg per U-100 insulin-syringe unit).
Store refrigerated at 2-8 °C and draw the prescribed units per dose: 250 mcg = 25 units, 500 mcg = 50 units, 1000 mcg = 100 units (one full 1 mL syringe).
Educational note: clinical ACE-031 was a weight-based subcutaneous biologic (0.02-3 mg/kg, equivalent to tens of milligrams per dose in an adult) given every 2-4 weeks; these small fixed research doses and the reconstitution scheme are an educational measurement reference only — the program was discontinued and ACE-031 is not for human use.
Interactive ACE-031 Syringe Calculator
Currently visualizing the 1 mg vial reconstituted with 1 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 1mg dry powder in 1mL water yields 1.00 mg/mL. To evaluate a 250mcg dose, pull to 25.0 units (25 syringe ticks).
U-100 Syringe Representation
Educational reference visual. Assumes standard U-100 insulin syringe where 1.0 mL volume = 100 units.
Titration & Dose Escalation Schedules
| Phase | Dose per injection | Units (per injection) |
|---|---|---|
| Weeks 1-2 — initiation | 250 mcg | 25 units (0.25 mL) |
| Weeks 3-6 — build | 500 mcg | 50 units (0.50 mL) |
| Week 7+ — research maintenance | 1000 mcg (1 mg) | 100 units (1.00 mL) |
Administration guidelines: Refer to guidelines | 1 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 1 mg vial.
Peptide Vials (ACE-031, 1 mg each):
- check8 weeks at 250 mcg/week ≈ 2 vials (2 mg total)
- check12 weeks at 500 mcg/week ≈ 6 vials (6 mg total)
- check16 weeks at 1000 mcg/week ≈ 16 vials (16 mg total)
- checkEach reconstituted 1 mg vial holds one full 1000 mcg dose, two 500 mcg doses, or four 250 mcg doses; discard refrigerated solution after ~2-4 weeks as a fusion protein loses stability
Insulin Syringes (U-100):
- checkOnce-weekly dosing: 1 syringe per injection
- check8 weeks ≈ 8 syringes; 12 weeks ≈ 12 syringes; 16 weeks ≈ 16 syringes
- checkEven the 1000 mcg maintenance dose (100 units) fits in a single 1 mL syringe, so no splitting is needed
Bacteriostatic Water (30 mL bottles): Use 1 mL per 1 mg vial for reconstitution.
- check8 weeks (2 vials) ≈ 2 mL
- check12 weeks (6 vials) ≈ 6 mL
- check16 weeks (16 vials) ≈ 16 mL — one 30 mL bottle covers an entire course
Alcohol Swabs:
- check1-2 swabs per dose (vial top + injection site)
- check8 weeks ≈ 8-16 swabs; 12 weeks ≈ 12-24 swabs
- check16 weeks ≈ 16-32 swabs; keep extras for re-swabbing multi-use vials
Mechanism of Action (MOA)
ACE-031 is a recombinant dimeric fusion protein built from the extracellular ligand-binding domain of the human activin receptor type IIB (ActRIIB, gene ACVR2B) genetically linked to the Fc region of human immunoglobulin G1 (IgG1) [1][3]. It is not a small peptide; it is a roughly 80-100 kDa biologic. The Fc portion gives it a long circulating half-life and the soluble ActRIIB portion gives it function. Crucially, because the receptor domain is detached from any cell membrane, it can bind ligands but cannot transduce a signal — it behaves as a soluble decoy receptor, or \"ligand trap.\"\n\nMechanistically, ACE-031 intercepts members of the TGF-beta superfamily that normally signal through activin type II receptors. Its highest-affinity target is myostatin (GDF-8), the dominant negative regulator of skeletal muscle mass, but it also binds activin A, activin B, GDF-11, and the bone morphogenetic proteins BMP9 and BMP10 [3]. By sequestering myostatin and activins in the circulation, ACE-031 lifts the normal brake on muscle, increasing fiber size and lean mass. Se-Jin Lee's group showed that a soluble ActRIIB construct of this type can increase mouse muscle mass by up to about 60% within two weeks and that the effect requires blockade of multiple ligands, not myostatin alone [3].\n\nPharmacokinetics: After subcutaneous injection, ACE-031 is absorbed slowly with first-order kinetics, reaching peak plasma concentration (Tmax) at roughly 5-7 days; mean AUC and Cmax rise linearly with dose, and the mean elimination half-life is approximately 10-15 days [1]. That long half-life is why clinical protocols dosed only every 2-4 weeks rather than daily or weekly. Pharmacodynamically, a single 3 mg/kg dose in healthy postmenopausal women increased total-body lean mass by 3.3% (DXA) and thigh muscle volume by 5.1% (MRI) by day 29, alongside biomarker shifts indicating increased bone formation, decreased bone resorption, and changes in fat metabolism [1].\n\nThe same broad ligand promiscuity that makes ACE-031 powerful also explains why it was discontinued. ActRIIB binds BMP9 and BMP10, which are essential regulators of vascular endothelium. Trapping them produced dose-related vascular events — epistaxis (nosebleeds), gum bleeding, and cutaneous telangiectasia (dilated small vessels) — in healthy adults and in boys with Duchenne muscular dystrophy, prompting a clinical hold in 2011 and permanent discontinuation by Acceleron and Shire in 2013 [2][6].\n\nThe real-world route is subcutaneous injection of a weight-based dose; the fixed-microgram reconstitution scheme on this page is an educational measurement convention used across this site, not a clinically validated delivery method. ACE-031 is not approved by any major regulator and exists only as a discontinued investigational agent and a grey-market research chemical [6].
Clinical Trial Efficacy Highlights
- starAttie and colleagues (2013, Muscle & Nerve) ran the pivotal Phase 1 single-ascending-dose study: 48 healthy postmenopausal women received one subcutaneous dose of ACE-031 (0.02-3 mg/kg) or placebo (3:1). A single 3 mg/kg dose increased total-body lean mass by 3.3% (P = 0.03, DXA) and thigh muscle volume by 5.1% (P = 0.03, MRI) by day 29, with serum markers showing increased bone formation, decreased bone resorption, and reduced fat metabolism markers [1].
- starIn the same Phase 1 study, ACE-031 absorption followed first-order kinetics with a median Tmax of about 5-7 days, mean AUC and Cmax increasing linearly with dose, and a mean elimination half-life of roughly 10-15 days — pharmacokinetics that justified the every-2-to-4-week clinical dosing interval and that distinguish this Fc-fusion biologic from short-acting peptides [1].
- starLee and colleagues (2005, PNAS) provided the mechanistic proof of concept: a soluble ActRIIB receptor construct of the same class increased skeletal muscle mass in wild-type mice by up to about 60% within two weeks, and demonstrated that simultaneous blockade of multiple activin type II receptor ligands (myostatin plus activins/GDF-11) is required for maximal hypertrophy [3].
- starCampbell and colleagues (2017, Muscle & Nerve) conducted the randomized, double-blind, placebo-controlled ascending-dose Phase 2 trial in ambulatory boys with Duchenne muscular dystrophy, using cohorts of 0.5 mg/kg subcutaneously every 4 weeks and 1 mg/kg every 2 weeks. Investigators observed non-significant trends toward maintained 6-minute walk distance, increased lean body mass, increased bone mineral density, and reduced fat mass, but the study was halted after the second dosing regimen for safety [2].
- starThe Duchenne trial was stopped specifically because of dose-related vascular bleeding events — epistaxis and cutaneous telangiectasia — rather than for lack of efficacy; the muscle and body-composition trends were considered promising but could not be pursued because of the safety signal [2].
- starThe Phase 1 program in healthy postmenopausal women was formally registered as NCT00952887 (a safety, tolerability, pharmacokinetic and pharmacodynamic study of ACE-031), and the Duchenne program as NCT01099761, documenting the subcutaneous, weight-based, every-2-to-4-week dosing strategy used throughout ACE-031 development [4][5].
- starThe Muscular Dystrophy Association reported that ACE-031 trials were placed on clinical hold in February 2011, publicly halted in April 2011, and the Acceleron/Shire collaboration was permanently discontinued in May 2013; the bleeding and telangiectasia events were described as resolving fully after treatment was stopped [6].
- starCadena and colleagues (2025) reported that ACE-031 increased muscle mass and strength in the common marmoset (Callithrix jacchus), extending the anabolic effect of soluble ActRIIB blockade into a nonhuman primate model and reinforcing the muscle-growth mechanism seen in rodents and early human data [7].
Side Effects & Tolerability Profile
Clinical subjects transiently report mild side effects. Slowly escalating the titration dose represents the single most effective intervention to limit side effects.
- warningVascular bleeding events were the defining safety problem and the reason development stopped: dose-related epistaxis (nosebleeds), gum/gingival bleeding, and cutaneous telangiectasia (small dilated skin vessels) occurred in both healthy adults and boys with Duchenne muscular dystrophy [2][6].
- warningThese vascular effects are attributed to off-target trapping of BMP9 and BMP10, two TGF-beta ligands essential for endothelial and vascular integrity that ActRIIB also binds; this is an on-mechanism, not idiosyncratic, risk of broad ActRIIB ligand traps [3].
- warningInjection-site reactions, particularly erythema at the subcutaneous site, were reported in the Phase 1 study even though the drug was otherwise generally well tolerated [1].
- warningAs a human IgG1 Fc fusion protein, ACE-031 carries an inherent risk of immunogenicity (formation of anti-drug antibodies) that can reduce exposure or, in principle, cause hypersensitivity; this is a general class risk for biologic ligand traps.
- warningBecause ActRIIB binds activins that regulate the reproductive (FSH) and other endocrine axes, broad activin blockade has the theoretical potential to perturb reproductive hormones and other activin-dependent pathways; long-term human endocrine safety was never established.
- warningBody-composition and skeletal effects (shifts in bone formation/resorption markers and fat metabolism) accompany the muscle effect, so off-target metabolic and bone consequences cannot be excluded with chronic use [1].
- warningACE-031 is on the WADA Prohibited List under the agents-affecting-myostatin category (S4.5) and is banned in sport at all times; using it for performance enhancement is prohibited and detectable.
- warningRegulatory/research status: ACE-031 is NOT approved by the FDA, EMA, or any major regulator; its clinical development was discontinued in 2013, no pharmaceutical-grade product exists, and grey-market "ACE-031" is an unregulated research chemical of unverified identity and purity. This page is educational only and not medical advice.
Subcutaneous Injection Technique
Most research peptides require subcutaneous injection into fatty tissue. Never inject directly into a blood vessel or deep muscle tissue unless clinically detailed.
1. Site Selection
Common locations include the abdomen (2 inches from navel), outer upper arms, or thighs.
2. Sanitization
Thoroughly clean the selected site, stopper and vial top using 70% isopropyl alcohol prep swabs.
3. Angle & Push
Pinch the skin and insert the needle at a 45 to 90-degree angle. Depress plunger smoothly.
4. Site Rotation
Rotate injection sites continuously to avoid lipodystrophy or tissue scarring.
Frequently Asked Questions
What is the typical ACE-031 dosage?expand_more
In published human trials the ACE-031 dosage was weight-based and subcutaneous: 0.02-3 mg/kg every 2-4 weeks. Measurable increases in lean mass and thigh muscle volume appeared only at the highest single 3 mg/kg dose in healthy postmenopausal women, while the Duchenne trial used 0.5 mg/kg every 4 weeks and 1 mg/kg every 2 weeks. Grey-market research vials are typically 1 mg and dosed as small fixed amounts (roughly 0.25-1 mg), which sit at or below the lowest clinical dose and far below the dose that actually changed muscle endpoints. There is no approved or established human dose; this page is educational only.
Is ACE-031 FDA approved?expand_more
No. ACE-031 (ramatercept) is not approved by the FDA, the EMA, or any other major regulator for any indication. It was developed by Acceleron Pharma with Shire for Duchenne muscular dystrophy but was placed on clinical hold in 2011 and permanently discontinued in 2013 after vascular bleeding side effects (nosebleeds, gum bleeding, skin telangiectasia). It is also prohibited in sport by WADA. Any ACE-031 sold today is an unregulated research chemical, and this page is educational, not medical advice.
What is the half-life of ACE-031?expand_more
ACE-031 has a long elimination half-life of approximately 10-15 days, measured in the Phase 1 single-ascending-dose study. After subcutaneous injection it is absorbed slowly, reaching peak plasma levels (Tmax) at about 5-7 days, with AUC and Cmax rising linearly with dose. The long half-life comes from the IgG1 Fc portion of the fusion protein and is the reason clinical trials dosed only every 2-4 weeks rather than daily or weekly.
How is ACE-031 reconstituted and administered?expand_more
Clinically, ACE-031 was given by subcutaneous injection of a weight-based dose. For the educational model on this site, a 1 mg vial is reconstituted with 1.0 mL of bacteriostatic water to give 1 mg/mL (10 mcg per U-100 insulin-syringe unit). Draw the water slowly down the vial wall and swirl gently — never shake, because the Fc fusion protein can foam and aggregate — then refrigerate at 2-8 °C. At that concentration 250 mcg = 25 units, 500 mcg = 50 units, and 1000 mcg = 100 units (one full syringe).
Why was ACE-031 discontinued, and is it safe?expand_more
ACE-031 was discontinued because its broad ligand trapping also blocked BMP9 and BMP10, two proteins essential for blood-vessel integrity. This produced dose-related vascular bleeding events — nosebleeds, gum bleeding, and skin telangiectasia — in both healthy adults and boys with Duchenne muscular dystrophy, triggering a 2011 clinical hold and permanent discontinuation in 2013. The events reportedly resolved after stopping treatment, but long-term safety was never established, no pharmaceutical-grade product exists, and ACE-031 is not considered safe or approved for human use.
Related Guides & Tools
Step-by-step references for reconstituting, measuring, and storing ACE-031, plus the universal dosing calculator.
Academic References & Study Citations
Attie KM, Borgstein NG, Yang Y, Condon CH, Wilson DM, Pearsall AE, Kumar R, Willins DA, Seehra JS, Sherman ML. A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers. Muscle Nerve. 2013;47(3):416-423. View Scientific Paper →
Campbell C, McMillan HJ, Mah JK, Tarnopolsky M, Selby K, McClure T, Wilson DM, Sherman ML, Escolar D, Attie KM. Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: results of a randomized, placebo-controlled clinical trial. Muscle Nerve. 2017;55(4):458-464. View Scientific Paper →
Lee SJ, Reed LA, Davies MV, Girgenrath S, Goad ME, Tomkinson KN, et al. Regulation of muscle growth by multiple ligands signaling through activin type II receptors. Proc Natl Acad Sci U S A. 2005;102(50):18117-18122. View Scientific Paper →
ClinicalTrials.gov. A Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of ACE-031 in Healthy Postmenopausal Women (NCT00952887). U.S. National Library of Medicine. View Scientific Paper →
ClinicalTrials.gov. A Phase 2 Study of ACE-031 in Subjects With Duchenne Muscular Dystrophy (NCT01099761). U.S. National Library of Medicine. View Scientific Paper →
Muscular Dystrophy Association (Quest). UPDATE: ACE-031 Clinical Trials in Duchenne MD. (Clinical hold February 2011; trials halted April 2011; collaboration discontinued May 2013.) View Scientific Paper →
Cadena SM, Bogdanovich S, Khurana TS, et al. ACE-031, a soluble activin type IIB receptor, increases muscle mass and strength in the common marmoset (Callithrix jacchus). 2025. View Scientific Paper →